Y. Cha, K. Shin, K. Lim, K. Yu, I. Jang
Department of Clinical Pharmacology & Therapeutics, Seoul National University College of Medicine & Hospital, Seoul, Korea
Objectives: Etanercept is a soluble recombinant human tumor necrosis factor receptor (TNFR) fusion protein which is used for the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriasis and other inflammatory diseases. A model characterizing the population pharmacokinetics (PK) of etanercept was explored. The aim of this study was to evaluate the relationships between PK parameters and explanatory covariates of etanercept in healthy Koreans.
Methods: Plasma concentration data from 35 individuals receiving single dose of etanercept (Enbrel®) 25 mg by subcutaneous injection into the abdomen were used. A total of 476 concentration data obtained before dosing and 3, 6, 12, 24, 36, 48, 60, 72, 96, 144, 216, 312 and 480 hour after drug injection. The population PK analysis was conducted using nonlinear mixed effect modeling approach NONMEM® (version 6.2) based on the plasma concentrations. The first order conditional estimation (FOCE) with interaction method was employed to fit the model run. The demographic characteristics including age, weight, and height were examined as covariates.
Results: A two compartment disposition model with first-order absorption and elimination was best characterized the PKs of etanercept. The parameter estimates of central volume of distribution (V/F), oral clearance (CL/F), inter-compartment clearance (Q), and peripheral volume of distribution (V2) were, 8.65 L, 0.0837 L/h, 0.431 L/h, and 3.34 L, respectively. The influence of covariates on PK parameters was insignificant.
Conclusions: PK model for etanercept was developed in healthy Korean population. The PKs of etanercept was adequately fitted by a two-compartment model with first-order absorption and elimination. This PK model can be used for PK-PD modeling studies to predict etanercept exposure and time course of clinical improvement in Korean patients.
Reference: PAGE 21 (2012) Abstr 2403 [www.page-meeting.org/?abstract=2403]
Poster: Other Drug/Disease Modelling